tbuckley/cabot-search huggingface dataset:
Abstract 13105: The Effect of Mechanical Stress on Cardiac Fibroblasts in Pulmonary Arterial Hypertension
Authors: Fjodor T Bekedam, Marisa C Smit, Anton Vonk Noordegraaf, Harm J Bogaard, Marie Jose Goumans, Frances S De Man, Aida Llucia-Valldeperas
Journal: Circulation (2022)

Introduction: Pulmonary arterial hypertension (PAH) is a rare fatal disease with vascular remodeling leading to increased right ventricular pressure followed by fibrosis. To study PAH-induced cardiac fibrosis we develop an in vitro model of the failing right ventricle, for which cardiac fibroblasts (cFBs) were generated from healthy subjects’ and PAH patients’ induced pluripotent stem cells (iPSC). Methods: Confluent iPSC were induced to differentiate by adding 12 μM CHIR99021 for 24h to RPMI supplemented with B27 without insulin. Next, cells recovered for 24 h in RPMI supplemented with B27 without insulin, followed by stimulation with 75 ng/ml FGF2 up to day 20. Finally, the differentiated cells were reseeded and submitted to 10% cyclic stretch at 1 Hz for 4 days using the Flexcell FX-6000 system. Control and PAH cFBs were characterized at gene and protein levels. Results: The differentiated cells had a spindle morphology typical of FBs. Furthermore, the presence of cardiac ( GATA4, TCF21 ) and fibroblast ( VIM, PDGFRα, COL1A1 ) markers at gene and protein levels confirmed the cFB identity. Comparable expression of fibroblast related genes was observed in PAH cFBs as well as controls. Over 4 weeks of culture, iPSC-cFBs increasingly expressed markers of activated FBs ( ACTA2 and POSTN) over time, similar to in vitro adult cFBs. When exposed to mechanical stretch, cell aligned to the stretch direction. Surprisingly, no increase in gene expression of extracellular matrix ( COL1A1, COL3A1 ) or activated fibroblasts ( ACTA2, POSTN ) markers was observed . Interestingly, under static and stretch conditions expression of these genes was increased in PAH cFBs compared to healthy cells. Conclusion: The cellular morphology after differentiation as well as the gene and protein analyses indicate that cFBs were successfully generated. Furthermore, cyclic stretch induced alignment of the cells but was not sufficient to stimulate fibroblast activation in either PAH or healthy cFBs.
Abstract 13925: Initial Triglyceride Glucose Index as a Predictor of No-Reflow After Primary Percutaneous Coronary Intervention
Authors: Mahmoud Abdelnabi, Yehia Saleh, Juthipong Benjanuwattra, Gaspar Del Rio-Pertuz, Natnicha Leelaviwat, Abdallah Almaghraby
Journal: Circulation (2022)

Introduction: The triglyceride glucose (TyG) index is a screening method for insulin resistance that can be used on a daily clinical basis and only requires two laboratory determinations: serum triglycerides and serum glucose. Prospective studies of predictive values of the TyG index for cardiovascular diseases (CVD) have primarily focused on pre-existing coronary arterial disease or diabetes mortality, and the TyG index has been shown to be associated with subclinical atherosclerosis symptoms, such as arterial stiffness and preclinical coronary arterial calcification. The study aimed to investigate the possible correlation between the TyG index and the no-reflow phenomenon in patients presented with acute STEMI undergoing primary percutaneous coronary intervention (PPCI). Methods: A total number of 702 patients who presented with acute STEMI in the period from 1/9/2015 to 1/9/2019 who underwent PPCI according to the standard techniques were included. Patients with a previous history of diabetes, dyslipidemia, or on statin therapy were excluded from the study. Initial triglyceride levels as well as fasting blood glucose were tested in all patients at the time of admission. TyG index was calculated for all patients. No-reflow was defined as distal Thrombolysis in Myocardial Infarction (TIMI) flow less than III. Results: 618 patients (88 %) had normal flow while 84 patients (12%) had no-reflow. The mean TyG index was 4.3±0.4 in the no-reflow group versus 4.2±0.4 in the normal reflow group (P = 0.03). After propensity matching, the mean TyG index was 4.2 ± 0.3 in both groups. (P = 0.99) Conclusion: In a retrospective observational study, there was no statistically significant difference between no-reflow and normal flow groups after propensity matching. Further research is required to detect whether the TyG index can be used as a readily available independent predictor of cardiovascular morbidity and mortality.
Abstract 14051: QRS Duration After Pulmonary Valve Replacement in Adults With Repaired Tetralogy of Fallot: Prediction of Ventricular Arrhythmias and Correlation With Right Ventricular Size
Authors: Rody Bou Chaaya, Emily Barron, Jeremy Herrmann, John Brown, Georges Ephrem
Journal: Circulation (2022)

Background: Tetralogy of Fallot (ToF) patients face complications such as heart failure and ventricular arrhythmias (VA) after early repair which may be mitigated by pulmonary valve replacement (PVR). Prior studies have shown significant decreases in QRS duration and right ventricular (RV) size following PVR. We aimed to determine whether QRS duration reduction independently identifies patients at lower risk of VA and/or correlates with a decrease of RV size on cardiac magnetic resonance imaging (CMR) with long-term follow-up. Methods: We retrospectively identified patients ≥18 years old with repaired ToF who underwent surgical or transcatheter PVR, respectively, at our tertiary care center. Demographics, imaging, and ECGs (pre-PVR, 30 days to 1-year post-PVR, and closest to follow up CMR) were collected. Patients with ventricularly paced rhythm were excluded. The composite primary outcome was defined as sustained VT, ICD shock for sustained VT or inducible VT on EP study. Results: During the study period, 85 patients were included (median follow-up 3.6 years; median age 34 years; 51% females, 68% surgical PVR and median LVEF 56%). The primary outcome was observed in 8 (9.6%) patients. QRS duration decreased by 5 ms (pre-PVR mean 154±28 ms to 149±28ms post-PVR; p=0.0001). Increased age at PVR (OR 1.1 per year), QRS≥180ms post-PVR, no reduction in QRS after PVR (ΔQRS ≤ 0ms), and a history of VT were significantly associated with the composite outcome. (Table) The change in QRS was linearly correlated with the change in RVEDVi (R = 0.66; p=0.002). Conclusion: In conclusion, adults with repaired ToF experience a reduction in QRS duration post-PVR. This change correlates with the change in the RV size post-operatively. A QRS ≥180ms post-PVR, no reduction in QRS, increased age at repair, and a history of VT independently predict the occurrence of VT post-PVR. Patients with these risk factors may warrant closer monitoring and/or ICD consideration.
Abstract 13469: A Risk Score Model to Identify Patients With High Likelihood of Left Main or 3-vessel Coronary Artery Disease
Authors: Lorenzo Braghieri, Essa Hariri, Maan Fares, Benico Barzilai, Wael A Jaber, Michael Rothberg
Journal: Circulation (2022)

Introduction: Revascularization improves outcomes only for stable coronary artery disease (CAD) patients with high-risk coronary anatomy (HRCA). While exercise stress test (EST) is the screening modality for CAD, identifying HRCA noninvasively is challenging. We aimed to derive a prediction model, incorporating clinical and EST characteristics, to screen for HRCA. Methods: We included adult patients who underwent EST followed by elective invasive coronary angiography (ICA) at our center between 2017 and 2019. HRCA was defined as left main (LM) or 3-vessel disease on ICA. Significant CAD was defined as ≥50% stenosis in the LM and/or ≥70% stenosis in the 3 main vessels. We excluded patients with acute coronary syndrome or ejection fraction &lt;50%. Variables with p&lt;0.1 at univariable analysis were selected as candidates to enter a multivariable stepwise backward regression model to derive a HRCA risk model. Results: 304 consecutive patients met inclusion criteria (64[13]years, 81.6% M). 15.5% were found to have HRCA on ICA. Median time from EST to ICA was 11[31]days. The following hit the threshold for inclusion into the multivariable model: hypertension, maximal predicted heart rate (MPHR), diabetes, rate pressure product, metabolic equivalents, exercise time, chronotropic response index ≥0.8, heart rate recovery, Duke Treadmill Score (DTS). After backward selection, hypertension (OR 17.08, p=0.008), MPHR (0.98, p=0.048), and very abnormal DTS (8.26, p=0.001) were the only significant predictors of HRCA ( Fig.1A ). The fully adjusted model showed good discrimination for HRCA (AUC 0.74, p&lt;0.001, Fig.1B ). Conclusions: In an era of declining emphasis on EST in favor of imaging stress test, we identified a risk model based on clinical and EST-derived parameters, that can accurately predict likelihood of HRCA, enabling personalized risk-stratification. Further studies are needed to externally validate our model.
Abstract 12926: Senescent CD8 T Cells are Enriched in Atherosclerotic Plaques From Patients With Type 2 Diabetes and Their Circulating Levels Are Normalized by Intensive Lipid Lowering
Authors: Natalia Eberhardt, Ravneet Kaur, Michael Gildea, Dayasagar Das, Letizia Amadori, Dawn Fernandez, Roza Shamailova, swathy sajja, Manila Jindal, Caron Rockman, Thomas Maldonado, Edward Fisher, Ira J Goldberg, Jeffrey Berger, Chiara Giannarelli
Journal: Circulation (2022)

Introduction: Senescence is a key driver of age-related chronic inflammatory diseases including type 2 diabetes (T2D). Senescent T cells lose their ability to control tissue homeostasis and present aberrant cytokine and cytotoxic responses that ultimately cause tissue damage. Atherosclerotic plaques from T2D present more severe pathology than patients with no diabetes (ND) and circulating senescent CD8 T cells are increased in T2D and associated with myocardial infarction. However, whether senescent CD8 T cells accumulate in atherosclerotic plaques of T2D patients is unknown. Hypothesis: Senescent T cells infiltrate atherosclerotic plaques and contribute to the aggravated cardiovascular risk in T2D. Methods: We performed unbiased scRNA-seq analysis (75,049 total cells) of plaques from T2D (n=12) and ND patients (n=10) enrolled in the Athero-In Study. Circulating immune cells from T2D (n=16) and ND (n=6) patients enrolled in the CHORD study were analyzed using mass cytometry (CyTOF) before and after lipid lowering treatment. Results: We found a cluster of CD8 T cells expressing a senescence gene signature ( B3GAT1, KLRG1, KLRF1), as well as proinflammatory ( IFNG, TNF, CCL4, CCL5 ) and cytotoxic ( GZMB, PRF1, GNLY ) genes. Plaque senescent CD8 T cells showed a terminally differentiated effector memory phenotype (TEMRA) with high expression of CX3CR1 and low expression of lymphoid-homing genes ( SELL, CCR7) . CyTOF analysis revealed that circulating senescent CD8+ CD28- CD57+ T cells were increased in T2D compared to ND patients. Treatment with PCSK9 inhibitor plus statin/ezetimibe, which reduced LDL levels by &gt;70% at 4 weeks, normalized senescent CD8 T cell frequency in T2D patients to the levels of ND subjects at baseline. No changes were observed in cells from cholesterol-reduced ND patients. Conclusions: Our results show that senescent CD8+ T cells are enriched in atherosclerotic plaques and blood of T2D patients. The observation that acute lipid lowering normalized circulating senescent CD8 T cells in T2D patients indicates that T cell senescence can be improved by more aggressive lipid control in high risk T2D subjects. Further analyses are needed to understand how T cell senescence contributes to atherosclerosis and impaired regression in T2D.
Abstract 14281: Direct-Current Cardioversion During Ablation Predicts Recurrence of Atrial Arrhythmia During Long-Term Follow-Up
Authors: Nektarios Vasilottos, Awaneesh Kumar, Chase King, Tanyanan Tanawuttiwat, John M Miller, Mithilesh Das
Journal: Circulation (2022)

Background: The predictive value of termination of atrial fibrillation (AF) with direct-current (DC) cardioversion (CV) during catheter ablation (CA) during a long-term follow-up is not known. Methods: We studied the long-term success of CV during ablation in patients who underwent catheter ablation of AF and followed them for recurrence of AF/atrial flutter (AFL). Results: Of 187 patients (male: 75%, mean age: 60.3 ± 10.7 years), 96 (51.3%) patients required DC cardioversion during the initial CA. A mean number of 1.4 ± 0.6 ablations (p=NS) were performed during follow-up in both groups. There were no significant differences in baseline characteristics including age, gender, race, body mass index, left ventricular ejection fraction, and presence of hypertension, diabetes, and valvular disease. During a median (±1SE) follow-up of 5.23 ± 0.17 years, a significantly higher percentage of patients who needed CV during CA had recurrence of AF/AFL as compared to patients who did not need CV to terminate AF during CA (39.6 vs 16.5%, p &lt; 0.001). Cox regression analysis confirmed DC cardioversion during ablation as a predictor of recurrence of AF/AFL at time of last follow-up (OR: 2.78, 95% CI 1.52 to 5.10, p &lt; 0.001). Kaplan-Meier survival analysis shows significantly decreased time to recurrence in patients who had CV during initial ablation than those who did not require DC cardioversion (log-rank p &lt;0.001). Conclusion: DC cardioversion during catheter ablation is a predictor for recurrence of AF/AFL during long-term follow-up.
Abstract 12977: Combined Coronary Stenting and Cutting Balloon Angioplasty in the Management of a Postpartum Spontaneous Coronary Artery Dissection
Authors: Alexander Somerville, Andrew Weinberg
Journal: Circulation (2022)

Introduction: Spontaneous coronary artery dissection (SCAD), whilst documented in the peripartum period, has limited data in regard to management with cardiac intervention. SCAD is typically managed conservatively; however, in cases of hemodynamic instability and persistent ischemia, cardiac intervention with percutaneous coronary intervention (PCI) or coronary artery bypass grafting can be considered. Case: We present the case of a 34-year-old G2P2 female, without significant past medical history, who initially presented with severe substernal chest pain, five days following a spontaneous vaginal delivery. Initial electrocardiogram revealed sinus bradycardia without ischemic changes. Troponin I was elevated to 0.22 and 0.24. Heparin infusion, Aspirin loading, and Metoprolol were initiated. Coronary catheterization was performed and revealed dissection of a large left circumflex artery dissecting distally into the first obtuse marginal (OM1). A drug eluting stent (DES) was placed to the OM1. However, this worsened the dissection hematoma, propagating distally to the second obtuse marginal (OM2), also treated with a DES. Cutting balloon angioplasty was performed on the proximal circumflex to fenestrate the dissection flap and prevent proximal propagation of the dissection. A third DES was placed to the proximal circumflex artery. The patient continued dual anti-platelet therapy (DAPT) for one year, without complication. Conclusions: SCAD, in a young postpartum female, is a rare and potentially catastrophic condition. We present a case of SCAD, managed with PCI. This case demonstrates both the risk of dissection propagation with coronary stenting, as well as potential risk mitigation with cutting balloon angioplasty. Figure 1. Coronary Catheterization with PCI. A , SCAD of Lateral Circumflex to OM1. B , Post-DES to OM1 with dissection propagation to OM2 . C , Post-DES to OM2. D , Post-Balloon angioplasty and DES to proximal lateral circumflex
Abstract 13088: Peak Systolic Strain Rate is Associated With Incident Heart Failure in the General Population - The Copenhagen City Heart Study
Authors: Frederikke A Vyff, Niklas D Johansen, Kristoffer G Skaarup, Mats H Lassen, gorm B jensen, Peter Schnohr, Rasmus Mogelvang, Tor Biering-Sørensen
Journal: Circulation (2022)

Introduction: Peak systolic strain rate (SrS) reflecting the maximal acceleration of the systolic deformation during systole derived from speckle tracking echocardiography has been demonstrated to be a significant predictor of cardiovascular outcomes in patients with myocardial infarction. However, the prognostic utility of SrS in individuals with low cardiovascular risk is unknown. Hypothesis: We hypothesized that SrS was associated with incident heart failure (HF) in the general population. Methods: The 5th Copenhagen City Heart Study is a prospective cohort study. All participants had echocardiography performed. Exclusion criteria were prevalent HF and inadequate image quality for SrS assessment. The multivariable Cox model included variables from the Atherosclerosis Risk In Communities (ARIC) HF risk score and left ventricular ejection fraction. Results: A total of 4,013 participants were included in the final study sample. The mean age was 56 years and 2,290 (57.1%) were female. The mean SrS was 1.11 s -1 . During a median follow-up of 5.4 years, 101 participants (3%) developed HF. In multivariable analysis, decreasing SrS was significantly associated with HF (HR 1.32 (95% CI: 1.12; 1.56) p= 0.001) per s -1 decrease) (Figure). The optimal cutoff value of SrS &lt; 1.028 s -1 was linked to a 4-fold risk of HF (HR 4.38 (95% CI: 2.92; 6.56). Incidence rate of HF was 2.4 per 1000 person-years (95% CI: 1.77; 3.36) when SrS ≥ 1.028 and 10.7 per 1000 person-years (95% CI: 8.35; 13.63) when SrS &lt; 1.028. The cutoff had a sensitivity of 63.4% (95% CI: 53.2; 72.7), a specificity of 72.1% (95% CI: 70.6; 73.5), and a negative predictive value of 98.7% (95% CI: 98.2; 99.1). Finally, SrS added incremental value to the ARIC HF risk score with a net reclassification index of 0.264 (95% CI: 0.086; 0.415). Conclusions: SrS was significantly associated with the development of HF in the general population and provided incremental value to the ARIC HF risk score.
Abstract 14840: Performance of Quality Measures for Patients With Heart Failure in a Learning Health System
Authors: Albert Y Liu, Alice Lu, Lucia Petito, Stephen D Persell, Lacey Gleason, Anna Pawlowski, Tingqing Wu, Anjan Tibrewala, Abel Kho, Justin D Smith, Raja K Mutharasan, Jane E Wilcox, Clyde W Yancy, Faraz S Ahmad
Journal: Circulation (2022)

Introduction: Distinguishing heart failure (HF) patients who have suboptimal care quality due to physiological limitations vs non-clinical reasons (i.e. clinical inertia) may facilitate deployment of limited resources in a learning health system. We sought to evaluate the impact of accounting for physiological limitations on quality measures (QMs) using electronic health record (EHR) data. Methods: We developed EHR-based QMs for guideline-directed medical therapies (GDMT) for patients with HF with reduced ejection fraction (HFrEF), adapted from the 2020 ACC/AHA report on quality measures. In a cohort of HFrEF patients from primary care and cardiology clinics at an integrated health system, we compared the 2021 monthly rate of prescription of beta blockers (BBs), ACEis/ARBs/ARNIs, mineralocorticoid receptor antagonist (MRAs), and SGLT2 inhibitors (SGLT2is), with and without available clinical exclusions based on vitals, renal function, and medical history. Results: A cohort of 4186 patients with HFrEF (mean age 69, 35% female, 18% Black) had at least one eligible encounter in 2021. The monthly prescription rates of GDMT were high for BBs (79.1-84.8%) and ACEIs/ARBs/ARNIs (69.1-77.0%), but low for MRAs (39.4-52.0%) and SGLT2is (6.9-23.2%). With the addition of clinical exclusions, the performance on each QM was higher for BBs (83.1-88.0%), ACEIs/ARBs/ARNIs (78.1-84.7%) MRAs (48.3-60.2%), and SGLT2is (8.8-28.7%) (Figure). Conclusions: The addition of EHR-based clinical exclusions resulted in higher QM performance and identified a narrower population that may benefit more from quality improvement strategies.
Abstract 13287: Reading Nutrition Labels, and Self-Regulatory Lifestyle Behaviors Improves Cardiovascular Health: A Structural Equation Modeling Approach - Nhanes 2017-2018
Authors: Vijaya Parameswaran, Yunmei Wang, Phillip Cola, Priya Nambisan, Rajesh Dash
Journal: Circulation (2022)

Introduction: Recommendations for self-regulatory lifestyle behaviors - SRLB, such as reducing salt, or calories, often focus on reading nutrition labels. While these are correlated with cardiovascular outcomes, their causal effects are underexplored. Hypothesis: As covariance-based structural equation modeling - SEM, examines multivariate causal relationships in one model while considering measurement error, we propose using SEM to hypothesize that label reading and SRLB will improve cardiovascular outcomes (Figure1a) Methods: SEM was applied to National Health and Nutrition Examination Study 2017 - 2018 data in adults over 18 years of age, adjusted for education, age, gender, and ethnicity. Label reading included the use of calorie and sugar information. SRLB included weight loss, increasing exercise, and reducing salt and fat. Results: Of 4260 adults, 51.9% were female, with a mean age of 51.46 ± 17.5 (Table 1b). Extensive effects of SRLB, on HDL-C (β= .12, p &lt;.01), Total Cholesterol - TC (β= -.17, p &lt;.001); and label reading, on Blood Pressure - BP (β = -.73, p &lt;.001), Triglycerides - TG (β = -.49, p &lt;.001) were noted. BMI (β = -.10, p &lt;.01) and Hba1c (β = -.13, P&lt;.001) improved with SRLB, but label reading showed no effect. Higher education increased BP (β =.1, P&lt;.001), but decreased Hba1c (β = -.07, P&lt;.001) and ethnicity had a negative effect on BMI (β = -.1, P&lt;.001) (Table 1c). Conclusions: Using SEM, we demonstrate the causal effects of dietary and lifestyle behaviors on cardiovascular outcomes. The extensive impact of label reading illustrates its efficacy in managing hypertension and dyslipidemia, but the absence of effect on weight and blood sugar management, and the varied effect of education, and ethnicity, need to be explored. In addition, our findings may underscore the need for culturally tailored lifestyle recommendations that achieve caloric balance by interpreting calorie and sugar information in the context of serving size and caloric expenditure.